US public support for vaccine donation to poorer countries in the 2009 H1N1 pandemic

Background: During the 2009 H1N1 pandemic, the global health community sought to make vaccine available "in developing nations in the same timeframe as developed nations." However, richer nations placed advance orders with manufacturers, leaving poorer nations dependent on the quantity and timing of vaccine donations by manufacturers and rich nations. Knowledge of public support for timely donations could be important to policy makers during the next pandemic. We explored what the United States (US) public believes about vaccine donation by its country to poorer countries. Methods and Findings: We surveyed 2079 US adults between January 22 nd and February 1 st 2010 about their beliefs regarding vaccine donation to poorer countries. Income (p = 0.014), objective priority status (p = 0.005), nativity, party affiliation, and political ideology (p<0.001) were significantly related to views on the amount of vaccine to be donated. Though party affiliation and political ideology were related to willingness to donate vaccine (p<0.001), there was bipartisan support for timely donations of 10% of the US vaccine supply so that those "at risk in poorer countries can get the vaccine at the same time" as those at risk in the US. Conclusions: We suggest that the US and other developed nations would do well to bolster support with education and public discussion on this issue prior to an emerging pandemic when emotional reactions could potentially influence support for donation. We conclude that given our evidence for bipartisan support for timely donations, it may be necessary to design multiple arguments, from utilitarian to moral, to strengthen public and policy makers' support for donations. © 2012 Kumar et al

An automated multiwell plate reading film microscope for live cell autofluorescence lifetime assays

Fluorescence lifetime imaging (FLIM) is increasingly used to read out cellular autofluorescence originating from the coenzyme NADH in the context of investigating cell metabolic state. We present here an automated multiwell plate reading FLIM microscope optimized for UV illumination with the goal of extending high content fluorescence lifetime assays to readouts of metabolism. We demonstrate its application to automated cellular autofluorescence lifetime imaging and discuss the key practical issues associated with its implementation. In particular, we illustrate its capability to read out the NADH-lifetime response of cells to metabolic modulators, thereby illustrating the potential of the instrument for cytotoxicity studies, assays for drug discovery and stratified medicine

Visualising apoptosis in live zebrafish using fluorescence lifetime imaging with optical projection tomography to map FRET biosensor activity in space and time

Fluorescence lifetime imaging (FLIM) combined with optical projection tomography (OPT) has the potential to map Förster resonant energy transfer (FRET) readouts in space and time in intact transparent or near transparent live organisms such as zebrafish larvae, thereby providing a means to visualise cell signalling processes in their physiological context. Here the first application of FLIM OPT to read out biological function in live transgenic zebrafish larvae using a genetically expressed FRET biosensor is reported. Apoptosis, or programmed cell death, is mapped in 3-D by imaging the activity of a FRET biosensor that is cleaved by Caspase 3, which is a key effector of apoptosis. Although apoptosis is a naturally occurring process during development, it can also be triggered in a variety of ways, including through gamma irradiation. FLIM OPT is shown here to enable apoptosis to be monitored over time, in live zebrafish larvae via changes in Caspase 3 activation following gamma irradiation at 24 hours post fertilisation. Significant apoptosis was observed at 3.5 hours post irradiation, predominantly in the head region

Transfer RNA-derived small RNAs in the cancer transcriptome

The cellular lifetime includes stages such as differentiation, proliferation, division, senescence and apoptosis.These stages are driven by a strictly ordered process of transcription dynamics. Molecular disruption to RNA polymerase assembly, chromatin remodelling and transcription factor binding through to RNA editing, splicing, post-transcriptional regulation and ribosome scanning can result in significant costs arising from genome instability. Cancer development is one example of when such disruption takes place. RNA silencing is a term used to describe the effects of post-transcriptional gene silencing mediated by a diverse set of small RNA molecules. Small RNAs are crucial for regulating gene expression and microguarding genome integrity.RNA silencing studies predominantly focus on small RNAs such as microRNAs, short-interfering RNAs and piwi-interacting RNAs. We describe an emerging renewal of inter-est in a‘larger’small RNA, the transfer RNA (tRNA).Precisely generated tRNA-derived small RNAs, named tRNA halves (tiRNAs) and tRNA fragments (tRFs), have been reported to be abundant with dysregulation associated with cancer. Transfection of tiRNAs inhibits protein translation by displacing eukaryotic initiation factors from messenger RNA (mRNA) and inaugurating stress granule formation.Knockdown of an overexpressed tRF inhibits cancer cell proliferation. Recovery of lacking tRFs prevents cancer metastasis. The dual oncogenic and tumour-suppressive role is typical of functional small RNAs. We review recent reports on tiRNA and tRF discovery and biogenesis, identification and analysis from next-generation sequencing data and a mechanistic animal study to demonstrate their physiological role in cancer biology. We propose tRNA-derived small RNA-mediated RNA silencing is an innate defence mechanism to prevent oncogenic translation. We expect that cancer cells are percipient to their ablated control of transcription and attempt to prevent loss of genome control through RNA silencing

Desynchronizing effect of high-frequency stimulation in a generic cortical network model

Transcranial Electrical Stimulation (TCES) and Deep Brain Stimulation (DBS) are two different applications of electrical current to the brain used in different areas of medicine. Both have a similar frequency dependence of their efficiency, with the most pronounced effects around 100Hz. We apply superthreshold electrical stimulation, specifically depolarizing DC current, interrupted at different frequencies, to a simple model of a population of cortical neurons which uses phenomenological descriptions of neurons by Izhikevich and synaptic connections on a similar level of sophistication. With this model, we are able to reproduce the optimal desynchronization around 100Hz, as well as to predict the full frequency dependence of the efficiency of desynchronization, and thereby to give a possible explanation for the action mechanism of TCES.Comment: 9 pages, figs included. Accepted for publication in Cognitive Neurodynamic

TGF-beta(2)- and H2O2-Induced Biological Changes in Optic Nerve Head Astrocytes Are Reduced by the Antioxidant Alpha-Lipoic Acid

Background/Aims: The goal of the present study was to determine whether transforming growth factor-beta(2) (TGF-beta(2))- and oxidative stress-induced cellular changes in cultured human optic nerve head (ONH) astrocytes could be reduced by pretreatment with the antioxidant alpha-lipoic acid (LA). Methods: Cultured ONH astrocytes were treated with 1.0 ng/ml TGF-beta(2) for 24 h or 200 mu M hydrogen peroxide (H2O2) for 1 h. Lipid peroxidation was measured by a decrease in cis-pari-naric acid fluorescence. Additionally, cells were pretreated with different concentrations of LA before TGF-beta 2 or H2O2 exposure. Expressions of the heat shock protein (Hsp) alpha B-crystallin and Hsp27, the extracellular matrix (ECM) component fibronectin and the ECM-modulating protein connective tissue growth factor (CTGF) were examined with immunohistochemistry and real-time PCR analysis. Results: Both TGF-beta(2) and H2O2 increased lipid peroxidation. Treatment of astrocytes with TGF-beta(2) and H2O2 upregulated the expression of alpha B-crystallin, Hsp27, fibronectin and CTGF. Pretreatment with different concentrations of LA reduced the TGF-beta(2)- and H2O2-stimulated gene expressions. Conclusion: We showed that TGF-beta(2)- and H2O2-stimulated gene expressions could be prevented by pretreatment with the antioxidant LA in cultured human ONH astrocytes. Therefore, it is tempting to speculate that the use of antioxidants could have protective effects in glaucomatous optic neuropathy. Copyright (C) 2012 S. Karger AG, Base

Combined In Silico, In Vivo, and In Vitro Studies Shed Insights into the Acute Inflammatory Response in Middle-Aged Mice

We combined in silico, in vivo, and in vitro studies to gain insights into age-dependent changes in acute inflammation in response to bacterial endotoxin (LPS). Time-course cytokine, chemokine, and NO2-/NO3- data from "middle-aged" (6-8 months old) C57BL/6 mice were used to re-parameterize a mechanistic mathematical model of acute inflammation originally calibrated for "young" (2-3 months old) mice. These studies suggested that macrophages from middle-aged mice are more susceptible to cell death, as well as producing higher levels of pro-inflammatory cytokines, vs. macrophages from young mice. In support of the in silico-derived hypotheses, resident peritoneal cells from endotoxemic middle-aged mice exhibited reduced viability and produced elevated levels of TNF-α, IL-6, IL-10, and KC/CXCL1 as compared to cells from young mice. Our studies demonstrate the utility of a combined in silico, in vivo, and in vitro approach to the study of acute inflammation in shock states, and suggest hypotheses with regard to the changes in the cytokine milieu that accompany aging. © 2013 Namas et al

Neutral Gauge Boson Contributions to the Dimuon Charge Asymmetry in B Decays

Recently, the D0 Collaboration measured the CP-violating like-sign dimuon charge asymmetry in neutral B decays, finding a 3.2sigma difference from the standard-model (SM) prediction. A non-SM charge asymmetry a_sl^s suggests a new-physics (NP) contribution to Bs-Bsbar mixing. In this case, in order to explain the measured value of a_sl^s within its 1sigma range, NP must be present in Gamma_12^s, the absorptive part of the mixing. In this paper, we examine whether such an explanation is possible in models with flavor-changing Z (ZFCNC) or Z' (Z'FCNC) gauge bosons. The models must also reproduce the measured values of the indirect CP asymmetry S_psi-phi in Bs -> J/psi phi, and Delta Gamma_s, the Bs-Bsbar width difference. We find that the ZFCNC model cannot reproduce the present measured values of S_psi-phi and a_sl^s within their 1sigma ranges. On the other hand, in the Z'FCNC model, the values of all three observables can be simultaneously reproduced.Comment: 18 pages, 7 figures, JHEP format. Some ZFCNC equations corrected, ZFCNC analysis redone, references added, conclusions unchange

Emergent versus delayed lithotripsy for obstructing ureteral stones: a cumulative analysis of comparative studies

Objective To analyze the current evidence on the use of ureteroscopy (URS) and extracorporeal shock wave lithotripsy (ESWL) for the management of obstructing ureteral stones in emergent setting. Methods A systematic literature review was performed up to June 2016 using Pubmed and Ovid databases to identify pertinent studies. The PRISMA criteria were followed for article selection. Separate searches were done using a combinations of several search terms: "laser lithotripsy", "ureteroscopy", "extracorporeal shock wave lithotripsy", "ESWL", "rapid", "immediate", "early", "delayed", "late", "ureteral stones", "kidney stones", "renal stones". Only titles related to emergent/rapid/immediate/early (as viably defined in each study) versus delayed/late treatment of ureteral stones with either URS and/or ESWL were considered for screening. Demographics and operative outcomes were compared between emergent and delayed lithotripsy. RevMan review manager software was used to perform data analysis. Results Four studies comparing emergent (n = 526) versus delayed (n = 987) URS and six studies comparing emergent (n = 356) versus delayed (n = 355) SWL were included in the analysis. Emergent URS did not show any significant difference in terms of stone-free rate (91.2 versus 90.9%; OR 1.04; CI 0.71, 1.52; p = 0.84), complication rate (8.7% for emergent versus 11.5% for delayed; OR 0.94; CI 0.65, 1.36; p = 0.74) and need for auxiliary procedures (OR 0.85; CI 0.42, 1.7; p = 0.85) when compared to delayed URS. Emergent ESWL was associated with a higher likelihood of stone free status (OR 2.2; CI 1.55, 3.17; p < 0.001) and a lower likelihood of need for auxiliary maneuvers (OR 0.49; CI 0.33, 0.72; p < 0.001) than the delayed procedure. No differences in complication rates were noticed between the emergent and delayed ESWL (p = 0.37). Conclusions Emergent lithotripsy, either ureteroscopic or extracorporeal, can be offered as an effective and safe treatment for patients with symptomatic ureteral stone. If amenable to ESWL, based on stone and patient characteristics, an emergent approach should be strongly considered. Ureteroscopy in the emergent setting is mostly reserved for distally located stones. The implementation of these therapeutic approaches is likely to be dictated by their availability.info:eu-repo/semantics/publishedVersio

Imbibition in Disordered Media

The physics of liquids in porous media gives rise to many interesting phenomena, including imbibition where a viscous fluid displaces a less viscous one. Here we discuss the theoretical and experimental progress made in recent years in this field. The emphasis is on an interfacial description, akin to the focus of a statistical physics approach. Coarse-grained equations of motion have been recently presented in the literature. These contain terms that take into account the pertinent features of imbibition: non-locality and the quenched noise that arises from the random environment, fluctuations of the fluid flow and capillary forces. The theoretical progress has highlighted the presence of intrinsic length-scales that invalidate scale invariance often assumed to be present in kinetic roughening processes such as that of a two-phase boundary in liquid penetration. Another important fact is that the macroscopic fluid flow, the kinetic roughening properties, and the effective noise in the problem are all coupled. Many possible deviations from simple scaling behaviour exist, and we outline the experimental evidence. Finally, prospects for further work, both theoretical and experimental, are discussed.Comment: Review article, to appear in Advances in Physics, 53 pages LaTe